Risk of Mania With Antidepressants

ACNP Task Force Report on SSRIs and Suicidal Behavior in Youth

“…The TADS Team (2004) study finds a slightly higher rate of mania-related symptoms (ie spontaneously reported mania, hypomania, and elevated mood) in the SSRI group (5/216; 2.3%) than the placebo group (1/112; 0.9%) (rates are too low to detect statistical significance), but no evidence of more restlessness and akathisia-like symptoms on fluoxetine compared to placebo, and the rate of emergence of such symptoms did not differ between fluoxetine and nonmedication groups in the course of treatment. Baldessarini et al (2005) report an elevated risk of mania in 5-14-year olds on SSRIs compared with tricyclics and in X5-year olds compared with untreated individuals. In those above 14 years of age, the risk was greater for tricyclic antidepressants compared with SSRIs.…”

Excessive Mood Elevation and Behavioral Activation with Antidepressant Treatment of Juvenile Depressive and Anxiety Disorders: A Systematic Review

“…Such activation responses have often been reported in association with AD treatment, and may be particularly likely among juvenile depressed patients who have not yet experienced a spontaneous episode of mania or hypomania, and are a clinically important basis of initially recognizing BPD in previously depressed patients [3,4,8,11,13,14,77,78]. The relatively high rates of excessive arousal-activation encountered seem inconsistent with typical exclusion of patients with known BPD from most AD trials [79], but are consistent with the view that BPD is not easily diagnosed in juveniles [59,60,80,81,82,83].…”

“…More recently, Martin et al [4] found evidence of mania-hypomania in 5.4% of over 87,000 mostly depressed young patients aged 5-29 years during treatment with an AD, and 3 times lower risks without such treatment. Risks were highest at ages 15-19 years and with tricyclic ADs after age 15, but with serotonin reuptake inhibitors among younger children [4,13]. …”

Bipolar Depression: An Orphan Syndrome?

“…Interestingly, however, many cases of "depression" (or anxiety disorder) are rediagnosed as bipolar disorder when hypomania or mania emerges during treatment. This phenomenon appears to be more probable with younger illness-onset, if only because bipolarity in older patients is likely to have been recognized earlier (13,36). An important, but still inadequately tested question is the extent to which drugs with proved (lithium) or putative (carbamazepine, lamotrigine, valproate) moodstabilizing or antimanic (antipsychotics) actions can prevent or minimize the severity of pathological moodelevation associated with antidepressant treatment in bipolar disorder.…”